The term "hemoglobinopathy" has been used to describe abnormalities of hemoglobin, such as sickle-cell disease. Most common are those of hereditary origin in which there is a substitution of one or more of the amino acids in the amino acid chains that form either the [.alpha]- or the ß-globin (alpha- and beta-globin) chains. Some of these genetic changes, such as the substitution of valine for glutamic acid that causes sickle-cell hemoglobin, are common in certain ethnic groups. Others are quite rare. Some hemoglobinopathies, such as those that produce sickle-cell disease and those that produce unstable hemoglobin, cause anemia. Other hemoglobinopathies result in a hemoglobin that does not carry oxygen efficiently, giving a brownish cast to the blood. Thalassemias such as "Mediterranean anemia" are sometimes classified as hemoglobinopathies, but differ in that they are characterized by quantitative deficiencies in hemoglobin chains, not abnormal chains.